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Publication : Reduction in alkaline sphingomyelinase in colorectal tumorigenesis is not related to the APC gene mutation.

First Author  Hertervig E Year  2003
Journal  Int J Colorectal Dis Volume  18
Issue  4 Pages  309-13
PubMed ID  12774245 Mgi Jnum  J:84197
Mgi Id  MGI:2665420 Doi  10.1007/s00384-002-0471-y
Citation  Hertervig E, et al. (2003) Reduction in alkaline sphingomyelinase in colorectal tumorigenesis is not related to the APC gene mutation. Int J Colorectal Dis 18(4):309-13
abstractText  BACKGROUND AND AIMS. The sphingomyelin pathway is an important intracellular mechanism in regulating cell growth. The first step in this pathway is catalysed by sphingomyelinases. Alkaline sphingomyelinase is specifically located in the intestinal tract. Markedly reduced alkaline sphingomyelinase activities have been found in sporadic colorectal tumours and in familial adenomatous polyposis adenomas. Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations. PATIENTS AND METHODS. Both germline and sporadic adenomatous polyposis coli gene mutations were studied. Alkaline, neutral, and acid sphingomyelinase activities were measured in the intestinal mucosa and content of multiple intestinal neoplasia mice, a murine model of familial adenomatous polyposis and compared to control mice. Alkaline sphingomyelinase activity was also measured in 11 human rectal tumors with APC gene mutation and compared with 9 control tumors without mutation. RESULTS. Alkaline, neutral, and acid sphingomyelinase activities were present in the small intestine and colon in both mice types with no differences in hydrolytic capacity or distribution pattern. In sporadic rectal tumors similar alkaline sphingomyelinase activities were identified in tumors with somatic APC gene mutations as in samples without mutations. In the tumors without detectable APC mutations beta-catenin was analyzed, but no mutation was detected. CONCLUSION. Alkaline sphingomyelinase is not directly linked to adenomatous polyposis coli gene mutations.
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